Cited by 2,864Cancer-related Molecular PathwaysCell death mechanisms and regulationT-cell and B-cell Immunology

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p53 is required for radiation-induced apoptosis in mouse thymocytes

Lowe, Scott W., Schmitt, Earlene M., Smith, Sallie W., Osborne, Barbara A., Jacks, Tyler·1993·Nature

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Abstract

The p53 tumour suppressor gene is the most widely mutated gene in human tumorigenesis. p53 encodes a transcriptional activator whose targets may include genes that regulate genomic stability, the cellular response to DNA damage, and cell-cycle progression. Introduction of wild-type p53 into cell lines that have lost endogenous p53 function can cause growth arrest or induce a process of cell death known as apoptosis. During normal development, self-reactive thymocytes undergo negative selection by apoptosis, which can also be induced in immature thymocytes by other stimuli, including exposure to glucocorticoids and ionizing radiation. Although normal negative selection involves signalling through the T-cell receptor, the induction of apoptosis by other stimuli is poorly understood. We have investigated the requirement for p53 during apoptosis in mouse thymocytes. We report here that immature thymocytes lacking p53 die normally when exposed to compounds that may mimic T-cell receptor engagement and to glucocorticoids but are resistant to the lethal effects of ionizing radiation. These results demonstrate that p53 is required for radiation-induced cell death in the thymus but is not necessary for all forms of apoptosis.

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Authors: Lowe, S. W., Schmitt, E. M., Smith, S. W., Osborne, B. A., & Jacks, T.
Affiliations: Massachusetts Institute of Technology (US)
University of Massachusetts Amherst (US)
ORCID: Lowe, Scott W.
Osborne, Barbara A.
Jacks, Tyler
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 1993-04
Volume: 362
Issue: 6423
Pages: 847-849
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/362847a0
OpenAlex: W2078581194
Cited by: 2,864
References: 44
Citations by year: 2026: 8 · 2025: 15 · 2024: 28 · 2023: 18 · 2022: 9 · 2021: 24 · 2020: 19 · 2019: 23 · 2018: 31 · 2017: 28 · 2016: 34 · 2015: 24 · 2014: 30 · 2013: 37 · 2012: 40
FWCI: 123.84
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords: p53, radiation-induced apoptosis, thymocytes, ionizing radiation, negative selection, T cell receptor signaling, glucocorticoids, T cell development, tumor suppressor, radioresistance (biology)
MeSH terms: Animals, Cells, Cultured, Dexamethasone, Gamma Rays, Mice, Inbred C57BL, Mutation, Thymus Gland, Genes, p53, Tumor Suppressor Protein p53, Apoptosis, Mice

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p53 is required for radiation-induced apoptosis in mouse thymocytes

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